Evaluating the influences of confounding variables on benchmark dose using a case study in the field of ionizing radiation.

Purpose: A vast amount of data regarding the effects of radiation stressors on transcriptional changes has been produced over the past few decades. These data have shown remarkable consistency across platforms and experimental design, enabling increased understanding of early molecular effects of radiation exposure. However, the value of transcriptomic data in the context of risk assessment is not clear and represents a gap that is worthy of further consideration.

In vitro exposure of human lens epithelial cells to X-rays at varied dose-rates leads to protein-level changes relevant to cataractogenesis.

Background: Accumulated body of evidence shows that ionizing radiation increases the risk of cataracts. The mechanisms are not clear and the International Commission on Radiological Protection indicates a need for research into understanding the process, particularly at low doses and low dose rates of exposure.

Purpose: This study was designed to examine protein-level modifications in a human lens epithelial (HLE) cell-line following radiation exposures.

Is there a role for the adverse outcome pathway framework to support radiation protection?

Purpose: In 2012, the Organization for Economic Cooperation and Development (OECD) formally launched the Adverse Outcome Pathway (AOP) Programme. The AOP framework has the potential for predictive utility in identifying early biological endpoints linked to adverse effects. It uses the weight of correlative evidence to identify a minimal set of measurable key events that link molecular initiating events to an adverse outcome.

In vitro toxicoproteomic analysis of A549 human lung epithelial cells exposed to urban air particulate matter and its water-soluble and insoluble fractions.

Background: Toxicity of airborne particulate matter (PM) is difficult to assess because PM composition is complex and variable due to source contribution and atmospheric transformation. In this study, we used an in vitro toxicoproteomic approach to identify the toxicity mechanisms associated with different subfractions of Ottawa urban dust (EHC-93).

Methods: A549 human lung epithelial cells were exposed to 0, 60, 140 and 200 μg/cm doses of EHC-93 (total), its insoluble and soluble fractions for 24 h.

Differential cytotoxic and inflammatory potency of amorphous silicon dioxide nanoparticles of similar size in multiple cell lines.

The likelihood of environmental and health impacts of silicon dioxide nanoparticles (SiNPs) has risen, due to their increased use in products and applications. The biological potency of a set of similarly-sized amorphous SiNPs was investigated in a variety of cells to examine the influence of physico-chemical and biological factors on their toxicity. Cellular LDH and ATP, BrdU incorporation, resazurin reduction and cytokine release were measured in human epithelial A549, human THP-1 and mouse J774A.

Responses of A549 human lung epithelial cells to cristobalite and α-quartz exposures assessed by toxicoproteomics and gene expression analysis.

In this study, we used cytotoxicity assays, proteomic and gene expression analyses to examine the difference in response of A549 cells to two silica particles that differ in physical properties, namely cristobalite (CR) and α-quartz (Min-U-Sil 5, MI). Cytotoxicity assays such as lactate dehydrogenase release, 5-bromo-2'-deoxyuridine incorporation and cellular ATP showed that both silica particles could cause cell death, decreased cell proliferation and metabolism in the A549 human lung epithelial cells. While cytotoxicity assays revealed little difference between CR and MI exposures, proteomic and gene expression analyses unveiled both similar and unique molecular changes in A549 cells.

Contrasting biological potency of particulate matter collected at sites impacted by distinct industrial sources.

Background: Industrial sources contribute a significant proportion of anthropogenic particulate matter (PM) emissions, producing particles of varying composition that may differentially impact health. This study investigated the in vitro toxicity of ambient PM collected near industrial sites in relation to particle size and composition.

Methods: Size-fractionated particles (ultrafine, PM, PM, PM) were collected in the vicinity of steel, copper, aluminium, and petrochemical industrial sites.

Proteomic changes in human lung epithelial cells (A549) in response to carbon black and titanium dioxide exposures.

Unlabelled: This study combined cytotoxicity assays with proteomic analysis to characterize the unique biological responses of the A549 human lung epithelial cell line to two physicochemically distinct respirable particles titanium dioxide (TiO) and carbon black (CB). Cellular LDH, ATP, BrdU incorporation and resazurin reduction indicated that CB was more potent than TiO. Proteomic analysis was done using 2D-GE and MALDI-TOF-TOF-MS.

Human lung epithelial cell A549 proteome data after treatment with titanium dioxide and carbon black.

Here, we have described the dataset relevant to the A549 cellular proteome changes after exposure to either titanium dioxide or carbon black particles as compared to the non-exposed controls, "Proteomic changes in human lung epithelial cells (A549) in response to carbon black and titanium dioxide exposures" (Vuong et al., 2016) [1]. Detailed methodologies on the separation of cellular proteins by 2D-GE and the subsequent mass spectrometry analyses using MALDI-TOF-TOF-MS are documented.

Lipid composition alters drug action at the nicotinic acetylcholine receptor.

We tested the hypothesis that membrane lipid composition influences drug action at membrane proteins by studying local anesthetic action at the nicotinic acetylcholine receptor (nAChR). Infrared difference spectra show that concentrations of tetracaine consistent with binding to the ion channel (<50 microM) stabilize a resting-like state when the nAChR is reconstituted into phosphatidylcholine membranes containing the anionic lipid, phosphatidic acid, but have no effect on the nAChR reconstituted into membranes lacking phosphatidic acid, either in the presence or absence of cholesterol. Concentrations of tetracaine above 200 microM lead to neurotransmitter site binding in all membranes.